The present invention concerns extracts of cells or tissue or their supernatants which can inhibit proliferation of cells or tissue. The invention also provides compositions comprising such extracts as well as pharmaceutical, cosmetic and agricultural uses of the compositions and extracts.
Dormancy is a phenomena which is found in representatives of the plant kingdom as well as the animal kingdom.
The germination of various grains and seeds comprising the necessary propagation organs is delayed under certain circumstances and yet the grains or seeds are capable of germinating after various periods of time. The period of time in which germination of such seeds may be delayed varies and depends both on intrinsic properties of the seed as well as on the nature and extremity of the environmental conditions. Seeds have been shown to be in dormancy for a few days, a year, several years and even for more than several centuries (as was discovered lately in the case of some nympheaceae and seeds of trees of the Leguminosae family (Shen-Miller, J., et al., American Journal of Botany. 82:1367-1380, 1995)).
In some cases, the capability to develop dormancy lies in the embryo envelopes. In such a case, the separation of the envelopes from the embryo, result in its immediate germination.
In other cases, chemical growth inhibitors capable of preventing germination are present in the embryo itself and thus even a bare embryo may remain dormant (such as in the case of Rosaceae plants such as Kerria, Peach, etc.).
In plants, a state of dormancy may be found in the whole plant or in one or more of its parts. Dormant plants are plants which have two main metabolic states in their growth cycle. In their dormant state, the plants"" metabolism is extremely low, and the plant growth process is significantly inhibited although differentiation of certain cells may occur. In their active state, the plants"" metabolism rate is higher, the cells divide and differentiate and there is significant growth of various parts of the plant. In some cases, the whole plant enters the dormant state. Such is the case in Narcissus plants in which during the dormant state the only remaining viable part is the bulb which is in its dormant state. In other cases, some parts of the plants may be active while other parts may be in dormancy such as, for example, is the case of apple trees.
Substances capable of inhibiting germination have also been shown to be present in the juice of fleshy fruits or in other plant organs which produce juice. Examples are tomatoes, grapes, kiwi, watermelon and grapefruit wherein pips present in the fruit do not germinate although their surroundings are suitable for germination due to the water within the fruit.
Several plant-derived substances having an effect on cell proliferation have been reported. For example, European Patent Application No. 0381514 describes compositions comprising both naturally derived as well as synthetically prepared sphingolipids which have growth inhibitory activity on various kinds of cells. Another well known plant-derived substance having an anti-mitotic effect on various kinds of human cells is the substance colchicine (Samson, F. E., A. Rev. Pharmac. Toxic 16:143 (1976)). The Narcissus alkaloid, pretazettine, was shown to have a cytotoxic effect on Rausher virus-carrier cells as well as anti-leukemic activity in leukemic mice although the predominant activity of the substance was shown to be an antiviral activity (Furusawa, E. et al., Chemotherapy, 26:36-45, (1980) and Furusawa, E. et al., Proc. Soc. Exp. Biol. Med. 152:186-191, (1976)). Utex europaezis seed extracts were shown to comprise a non glycoprotein lectin capable of reversibly inhibiting growth of certain lymphocytes as well as to inhibit the growth of various reticulo endothelial tumor cell lines (Pirofsky, B., et aL, Vox-Sano, 42:295-303, (1982) and Pirofsky, B., et al., J. Biol. Response Mod., 2:175-185, (1983)). Root extract of Panex ginseng was shown to decrease DNA synthesis measured by [H3]-thymidine incorporation of V 79 Chinese hampster lung cells. Another substance, Narciclasine obtained from bulbs of various Narcissus varieties was shown, amongst other of its activities, to inhibit growth of wheat kemal radicals (Ceriotti, G., et al, Tumors 53:359-371 (1967)). Bulbs of Pancratium littoral collected in Hawaii were found to contain a product designated pancratistatin capable of inhibiting growth of various neoplastic cell lines in vitro (Pettit, G. R., et al., J. Nat. Prod., 49:995-1002 (1986)).
Against this, many plant extracts having an opposite effect on cells, i.e., capable of augmenting their proliferation were also described such as, for example, the methanolic extract from the root of Scutellaria baicalensis georgi were shown to significantly augment the cellular activity of fibroblasts (Chung, C.P., et al, Planta-Med, 61:150-153, (1995)). Gibberellin-like growth substances were found in six different plant species having bulbs (Staby, G. L., Hort. Science, 399-400 (1970)). Several cytokinins which were found in roots that developed from Narcissus bulbs had an effect on bulb growth of the plants in which they were detected (Vanstaden, J. V., Pflanzenphysiol., 86:323-30 (1978)).
The phenomena of dormancy may also be found in the animal kingdom, for example, in the small crustacean Artemia salina (Finamore and Clegg Ln: The Cell Cycle, Academic Press Ed., 249-278, 1969). The natural environment of this marine crustacea is usually briny ponds. After fertilization, the early stages of development of artemia involve the formation of a blastula which then becomes a gastrula. Under severe environmental conditions such as dehydration (drought), the gastrula is capable of forming a cyst wherein the whole organism enters a dormancy phase. The dormant artemia gastrula (commonly miscalled xe2x80x9cartemia eggsxe2x80x9d) are capable of remaining in their dormant state for many years. When the encysted gastrula are rehydrated, the various metabolic activities of the artemia are resumed and protein synthesis can be seen after about 10 minutes. However, DNA synthesis and cell division are absent until about after 60 hours (Le Gal, Y, In: Biochinie Marine, (Ed. Masson) p. 176, 1988).
Various plant derived compositions (such as retinoic acid U.S. Pat. No. 5,438,073) and xcex1-hydroxy acids (Ditre, C. M., et al., J. Am. Acad Dermatol., 34:187-195, 1996)) as well as animal derived extracts have been proposed for use in the cosmetic field for stimulating the proliferation and renewal of epidermal cells. Such compositions were considered to be useful in the cosmetic field where it is accepted that the natural renewal process of epidermis is slowed down with aging. It is believed that removal of the outer surface with simultaneous stimulation of growth of new cells in the inner layers of the epidermis to divide and migrate to the outer surface, will result in skin renewal and in a younger skin appearance. However, it is also known and has been recently shown that the increase in cell division is a crucial factor in converting normal cells into premalignant or malignant cells (Ames, B. N. et al, Environ. Health Perspect101:35-44 (1993)).
It is also believed today that normal human and animal cells have a finite capacity to replicate. It has been shown that the number of mitotic events that cultured normal animal cells can undergo appear to be inversely related to the age of the donor from which they were obtained (Hayflick, L., Clin. Geriatr. Med., 1:15-27, (1985)). It has also been shown that cell cultures obtained from patients with accelerated aging syndromes undergo less replications than cell cultures obtained from age matched control individuals.
The following is the meaning of some terms of which will be used in the text below:
Dormancyxe2x80x94a state in which there is a marked decrease in the metabolic rate of cells or tissues resulting in the inhibition of growth and proliferation of the cells or tissue.
Dormansxe2x80x94substances naturally found in cells or tissue and which are capable of inducing cells or tissue to enter a state of dormancy or of maintaining the dormant state in cells or tissues that have already entered that state. The dormans may be obtained from a variety of plant parts which are capable of entering into a state of dormancy; from juice of various fruits which contain dormans capable of inhibiting germination of seeds within the fruit; from animals which are capable of entering a phase of dormancy in their life cycle, e.g. gastrula of certain crustaceans such as artemia or dafnia; etc. In some cases, the dormans are found within a dormant tissue, e.g. in a dormant seed or in the gastrula of artemia or dafnia; in other cases the dormans are found in a tissue surrounding the dorman tissue or organ, e.g. in a fruit juice surrounding a dormant seed.
Extractxe2x80x94At least one substance obtained by any of a variety of extraction methods known in the art. For example, the extract may be an aqueous extract, a glycolic extract an alcoholic extract, an oily extract, etc. The extract in accordance with the invention is obtained from cells or tissues from a part of a plant or animal capable of entering a state of dormancy. The cells or tissue may be obtained directly from the plant or animal and the extract may then be prepared therefrom. Alternatively, cell cultures may first be prepared from the plant or animal cells or tissues and then the cell cultures may be grown for various periods of time. In order to prepare an extract, the cells are then harvested from the cell cultures, the cells and their growth medium are separated and an extract may be prepared either from the cells themselves or from the growth medium (which will be referred to as xe2x80x9csupernatantxe2x80x9d) which contains substances secreted by the cells into their growth medium. Thus, the xe2x80x9cextract xe2x80x9d may be obtained directly from plant or animal tissue or from an animal or plant cell or tissue culture.
Dorman extractxe2x80x94an extract obtained from a plant cell or tissue, from fruit or from an animal cell or tissue which comprises dormans.
Enriched dorman preparation (EDP)xe2x80x94a preparation derived from a natural source which comprises dormans in a concentration larger than that which is found in a natural unprocessed extract. The EDP may be obtained by purification of a natural extract to obtain fractions which contained dormans in the larger concentration, e.g. by various chromatographic techniques, by filtration, etc., as well as by biological means including growing cells or tissue which are capable of producing dormans under conditions in which they produce dormans in relatively large quantities and collecting their secretion products. In order to determine whether a preparation is an enriched dorman preparation, the preparation may be assayed for a specific biological activity associated with dormans, as described below. EDP contains a substantially higher concentration of dormans as compared to the natural preparation, e.g. at least 1.5 folds, preferably 2 folds and typically at least 2.5 folds to the concentration of the dormans in the natural preparation.
Producer cells or producer tissuexe2x80x94cells or tissue which are capable of producing dormans which may thus be extracted therefrom.
Target cells or target tissuexe2x80x94cells or tissue which are contacted with dormans, in accordance with the invention and which thereby enter a state of inhibition of their growth or proliferation or maintain such a state as the result of contact with dormans.
Dorman analogxe2x80x94a substance, typically synthetic, which has a dorman-like activity in that it is capable of inducing dormancy in the same cells or tissue induced to dormancy by the dorman and which, in accordance with the invention, is also capable of inhibiting growth and proliferatin of target cells or tissue.
Dorman composition (DC)xe2x80x94a composition comprising, as active ingredient, an amount of dorman (e.g. as a dorman extract) or dorman analog effective in inhibiting growth and proliferation of target cells or tissue (xe2x80x9ceffective amountxe2x80x9d). A dorman composition may comprise a naturally derived EDP, a composition comprising synthetic dormans as well as dorman analogs.
Active Extract (AE)xe2x80x94extracts obtained from cells or tissues from a part of a plant or animal capable of entering a state of dormancy during the non dormant state.
In accordance with the invention, use is made of a dorman composition. The composition may be used for inhibiting proliferation of cells, particularly cells xenogeneic to the producer cells or tissue. By one preferred embodiment of the invention, the compositions are used in human medicine and cosmetics. In accordance with another embodiment, the compositions are used for controlling plant growth. By yet a further embodiment, the compositions of the invention are used in food preservation.
By one aspect of the invention there is thus provided a preparation capable of inhibiting proliferation of target cells or target tissues, comprising a member selected from the group consisting of:
(i) an extract obtained from producer cells or producer tissue, said cells or tissue originating in an organism capable of entering a phase of dormancy in at least one of its parts, said extract comprising at least one substance which induces or maintains said state of dormancy in an organism from which said producer cells or tissues are derived,
(ii) a dormancy inducing fraction of said extract; and
(iii) a dormancy inducing substance derived from said extract or fraction.
By one embodiment the composition comprises an enriched dorman preparation (EDP) which, as defined above, comprises dormans in a concentration larger than that which is found in a natural unprocessed extract.
The producer cells or tissues from which the extract is obtained may be of the same origin as said target cells or tissues but are preferably of a different origin. In accordance with one embodiment of the invention, said target cells or tissue are human cells or tissue and said producer cells or tissue are plant or non human animal cells or tissue. In accordance with another embodiment of the invention, said target cells or tissue are plant cells or tissue.
In accordance with one preferred embodiment of the invention, the dorman composition is a pharmaceutical or cosmetic composition for inhibiting cell proliferation within the body. In accordance with another embodiment of the invention, said composition is used for inhibiting germination of seeds (being either natural or artificially prepared) or growth of seedlings for the purpose of maintaining seedlings in a dormant state for example during storage. In accordance with a further embodiment of the invention, the dorman composition is used in fresh food preservation.
By one embodiment, the dormans or the extracts used in accordance with the invention are derived from dormant plants.
Compositions in accordance with the invention obtained from bulbs of dormant plants while in their dormant state are capable of inhibiting the growth of seedlings as well as to inhibit the proliferation of various target cells, including various mammalian cells, e.g. human cells, to a significantly higher extent than preparations obtained under the same conditions from bulbs of the same plan being in their active state. It was also found that dorman compositions obtained from cell cultures prepared from various parts of dormant plants and induced into dormancy are also capable of inhibiting the growth of seedlings as well as to inhibit the proliferation of various cells, including various mammalian cells, e.g. human cells. These DCs, in a wide range of concentrations, had no noticeable toxic effect on the target cells, this being in contrast to most substances which have an anti-proliferating effect.
In accordance with the invention, any plant capable of entering a dormant state may be used for obtaining an DC. Some non-limiting examples of such plants, as well as the parts of such plants which enter a dormant state (designated xe2x80x9cD-partxe2x80x9d) and from which the DC may be obtained, are shown in the following Tables I and II:
In accordance with the invention, DC is preferably obtained from plants which are in their dormant state either as a result of the natural process of dormancy or as a result of being externally induced into dormancy by exposure which induce a dormant state e.g. conditions as incubation at a dormancy inducing temperature for a sufficient period of time. The conditions for inducing dormancy in various dormant plants may vary (e.g. the incubation temperature and the duration of the incubation) and are known to a person versed in the art. Thus for example there are plants (such as Narcissus) induced into dormancy by their exposure to relatively high temperatures. Against this, other plants (such as tulip) will be induced into dormancy by their exposure to relatively low temperatures. Other factors such as light, humidity, concentration of various growth factors, etc. may also be used to induce dormancy.
In accordance with one preferred embodiment of the invention, the DC is obtained from a part of the plant capable of entering dormancy (D-part), e.g. from bulbs. Bulbs induced into their dormant state may either be used immediately for the preparation of DC or, alternatively, may be stored under conditions which maintain a dormant state, e.g. in the case of Narcissus these include high temperature and low humidity. In addition to bulbs, other parts of dormant plants such as combs, roots, seeds, etc., may also be induced into dormancy as explained above and then used for obtaining DC therefrom.
In accordance with another embodiment of the invention, the dorman extract is obtained from cell cultures which were prepared from any part of a dormant plant (e.g. bulbs) and induced into dormancy. The culture may be obtained by inoculation of bulbs of dormant plants having inflorescence stalk initials into a suitable medium to form callous cultures of the bulb extracts. The cell cultures are then typically grown to confluency and very small bulb parts are formed in the cell culture (termed xe2x80x9cbulbletsxe2x80x9d). Induction of a dormant state in the cell cultures or bulblets is obtained by their exposure to conditions which induce dormancy conditions, such as incubation at a dormancy inducing temperature for a sufficient period of time. Dormancy may also be induced in vitro by exposing the cell cultures or bulblets to various types of chemical stresses (low or high concentrations of sugar, salts, etc.).
In addition to bulblets, cell cultures derived from other parts of dormant plants such as combs, roots, seeds, etc., may also be used for obtaining cell culture derived dorman extracts.
By yet another embodiment, the dorman analogs of the invention may be synthetically prepared by any one of the methods known in the art such as by recombinant DNA techniques, chemical synthesis, , combinational chemistry, etc., the dorman analogs maintaining substantially similar characteristics as far as their ability to induce dormancy and inhibit proliferation of target cells of the dormans on which they are based.
Preferably, a plant derived DC of the invention is obtained as an aqueous extract of the plant material. The aqueous extract may be prepared by homogenizing the plant material and then suspending the homogenate in an aqueous solution. However, non aqueous plant extracts obtained by any one of the extraction methods known per se, may also at times be used in accordance with the invention.
In accordance with a further embodiment of the invention, the EDPs arc obtained from juice of fruits or other juice producing plant organs. Fruits typically contain dormans which inhibit germination of the seeds and pips while these are within the fruit. Examples of juices from which dormans may be purified are juice of citrus fruits, grapes, tomato, kiwi, etc. The fruit juice may be used as such or alternatively, the dormans can be purified from the fruit juice as explained below.
In accordance with yet another embodiment of the invention, the dormans are extracted from producer cells originating from animals capable of entering a dormant phase during their life cycle. During the dormant phase, the animals"" metabolic rate is lowered to a minimum and there is an arrest in cell proliferation. Examples of such animals are various marine crustacea such as artemia, dafnia and cyclops.
As explained above with regards to plant derived DC, animal derived DC may also be obtained from animals which are in their dormant state as a result of the natural process of dormancy or as a result of being externally induced into dormancy by exposure to dormancy-inducing conditions such as dehydration (Artemia salina) or anoxia (Artemiafranciscana). The dormans may be extracted from the animal tissue by various methods known per se.
The animal derived DC may be obtained from the animals or their organs as such. Alternatively, cell cultures may first be prepared from the dormant animal, and after maintaining the cells in culture for various periods of time, DC may then be extracted either from the supernatant or by harvesting the cells and/or extracting the DC therefrom.
The DC of the invention may be purified from the producer cells by a variety of methods known per se, for example by chromatography (e.g. TLC, HPLC, ion exchange) by size fractionation (e.g. dialysis, gel filtration), etc.
In accordance with the invention, it has been realized for the first time that, when administered to an individual, the anti-proliferative activity of said dorman composition may slow down the cell division rate of the cells present in the inner layers of the epidermis.
Another aspect of the invention is thus the use of said dorman compositions as a cosmetic or dermatological composition useful for talc maintenance of the juvenile appearance of an individual""s skin or for the treatment of age related skin changes.
In accordance with this latter aspect of the present invention, a dermatological or cosmetic composition is provided comprising from about 0.0001%, preferably from about 0.001%, typically from about 0.01% up to about 5% preferably up to about 1% by weight of dorman extract or dorman analog together with a dermatologically or cosmetically acceptable carrier.
The dermatological or cosmetic compositions of the invention may be administered in various forms such as in the form of a balm, an emulsified gel, an aqueous-alcoholic gel, anhydrous gel, an oil in water (O/W) type emulsion, a clear gel, cream containing liposomes, etc.
The cosmetic or dermatological compositions are typically topically administered. However, it may at times be advantageous to administer the compositions by other administration modes, such as, for example, by subcutane injections, by orally administered capsules or by iontophoresis (which involves the use of electric fields to increase the penetration of ionic active substances).
Due to their significant anti proliferative effect said dorman compositions may also be used for the treatment of various malignancies. As mentioned above, the cell division rate is a significant factor in determining the probability of a cell to become a premalignant or malignant cell. In addition, as known, the formation of a benign or malignant tumor is dependent, inter alia, on continuous divisions of the cells forming the tumor. Administration of the dorman compositions to an individual before the formation or at early stages of the formation of a benign or malignant tumor may result in the delay or prevention of the formation of a fully fledged tumor in the treated individual. Administration of said extracts to an individual suffering from a fully fledged benign or malignant tumor may result in the reduction of the tumor load in the treated individual and in the alleviation of the tumor-related symptoms. Said dorman compositions may be effective in the treatment of primary as well as secondary (metastatic) tumors. Said extracts may also be administered in combination with one or more known anti-tumorigenic treatments (e.g. chemotherapeutic agents, radiation etc.) to achieve a synergistic anti-tumorigenic effect. The doses of said extracts to be administered to an individual as well as the treatment modality will be dependent on characteristics of the treated individual (age, weight, medical history, etc.) as well as on characteristics of the developing or existing tumor (benign or malignant, size, origin, primary or secondary, etc.). In individuals having a high risk of developing a primary or secondary tumor, the dorman compositions may be administered routinely in order to reduce the probability of tumor formation.
The present invention thus further provides a composition comprising a dorman extract capable of inhibiting the proliferation of cells, for the administration to an individual having a benign or malignant tumor or being at a high risk of developing a tumor.
By yet an additional aspect of the invention, dorman compositions may be used to enhance the therapeutic index of chemotherapeutic and radiation treatments. In an individual receiving such treatments, normal dividing cells such as cells of the inner lining of the intestines, cells of hair follicles and hematopoietic cells are also harmed by the chemotherapeutic agents or radiation which are aimed at destroying the malignant cells of which a large percent are dividing cells. By administration of dorman compositions to an individual prior to or together with such treatments, it may be possible to inhibit the proliferation of a significant percent of the normal cells. As a result, toxic side effects due to the influence of the treatments on normal cells may be significantly reduced and when beneficial, higher concentrations of the chemotherapeutic or radiation treatments may be used. In order to facilitate the toxicity reducing affect of the dorman composition, it may at times be administered directly to a needing site, tissue or organ, e.g. onto the skin.
The present invention thus provides by a further of its aspects, a composition capable of inhibiting the proliferation of cells, for administration to an individual receiving chemotherapeutic or radiation treatments, comprising an effective amount of dorman, dorman extract or dorman analog.
Other therapeutic applications of the dorman compositions include inhibition of fibrosis, e.g. skin fibrosis, cirrhosis, and others. It should be noted that hitherto, fibrosis, which is an over proliferation of fibroblasts, has been treated by cytotoxic drugs, but with a limited application due to their general non specific toxicity. Inhibition of the fibroblast proliferation by the use of the dorman composition of the invention, provides a viable, less toxic alternative. In a similar manner, the dorman compositions of the invention may also be useful in the treatment of psoriasis which results from over proliferation of keratinocytes. Seborrheic keratosis, papilomas and warts may also be treated by the dorman compositions.
Another possible application of the dorman composition of the invention is in preservation of organs or tissue prior to their use for transplantation.
Other applications of said dorman compositions may be, for example, in the treatment of scalp baldness (Alopecia) which is many times one of the phenomenas associated with aging of the skin in an individual. In individuals suffering from Alopecia, the life span of scalp hair decreases substantially (e.g. from a life span of about 3 years in a normal individual to a life span of about one year in an individual suffering from Alopecia). Therefore, decreasing the rate of hair growth in an individual having a high probability of developing Alopecia or in an individual already showing for signs of scalp hair loss, will decrease the extent of such hair loss. Administration of the dorman compositions of the invention to such an individual may result in a partial or complete decrease of the hair loss. For this purpose, the dorman comprising compositions may be administered either topically at the site of scalp hair loss or, alternatively, in other cases may be administered systemically.
An additional phenomena which may be treated by administration of the dorman comprising compositions of the invention is associated with overgrowth of hair in various parts of an individual""s body, such as arms, back, etc. (Hirsutism). Such undesired overgrowth of hair appears many times in aging individuals and, at times, is associated with loss of scalp hair in the same individual. Due to their ability to reduce cell growth, compositions of the invention may be useful in reducing such undesired overgrowth of hair.
The amount of the dorman comprising compositions to be administered for the above two indications, the administration regimes as well as their mode of application will again depend both on characteristics of the treated individual (age, size, gender, etc.) as well as on parameters associated with the phenomena to be treated (such as the extent of scalp hair loss, the specific body parts in which there is overgrowth of hair, etc.).
In addition, the dorman composition may be useful as a complementary agent administered in combination with or following hair removal treatments such as, for example, shaving (where said extract may be incorporated in an aftershave solution) or hair stripping (e.g. by wax).
Another application of the dorman composition may involve its administration to an individual during the period in which a scar is formed, e.g. after an operation in order to decrease scar formation. By slowing down the rate of the healing process in such an individual, the final scar may be much less apparent. In addition, the anti-fibrotic effect of the dorman compositions decreases the formation of cheloids which commonly appear after healing.
The dorman composition may also be useful for extending the duration of a tan in an individual. Following exposure to the sun, epidermal cells comprise a high concentration of melanin. During skin renewal such melanin comprising cells are shed. By slowing down the cell renewal process in the skin, the dorman composition causes the melanin comprising cells and thus the tan to remain for a longer period of time.
In addition to inhibiting proliferation of various cells, said dorman compositions are also capable of slowing seed germination and inhibiting growth of various plant seedlings. Following germination of seeds, roots and hypocotyls begin to develop in the seedling. Incubation of the plant seedlings with the dorman composition results in the inhibition of the elongation of the seedling roots and hypocotyls. The dorman compositions may therefore be used for weed control, wherein their administration at an appropriate concentration may result in the inhibition of growth of non desirable weeds while not affecting the growth of the desired plant. In view of the natural origin of the dormans, their administration has no noticeable toxic effect on cells or tissue on which they are induced to act or on the environment. In addition, at times it may be useful to use such compositions for long term storage of seeds and seedlings.
The present invention thus provides a dorman composition having the activity of slowing and inhibiting the growth of plant seeds and/or seedlings comprising said dorman extract.
A further application of the dorman composition of the invention is in the preservation of fresh produce, e.g. vegetables, fresh fish eggs, fish shells, etc.
The invention also provides a process for the preparation of an anti-proliferative composition comprising mixing dormans or DC with a carrier so as to yield an anti-proliferative composition with an anti-proliferative effective amount of dormans in said composition. Such a prepared composition may be used, depending on the nature of the carrier, in therapy, cosmetics, food preservation or agriculture. Such a process for preparing a pharmaceutical or cosmetic composition typically comprises preparing an DC, and mixing it with an appropriate pharmaceutical or cosmetic acceptable carrier, the amount of DC being such so as to yield a final therapeutically or cosmetically (as the case may be) effective amount of dormans in the composition. Also provided is use of dormans or an DC for the preparation of such a pharmaceutical or cosmetic composition.
As will be appreciated, the various applications of the dorman composition of the invention given above, are examples of a myriad of possible applications of these compositions, all having in common the inhibition of proliferation of target cells.
In the following, the invention will be illustrated by some non-limiting examples with occasional reference to the figures.